Manipulating Ghrelin Signaling Via GOAT Inhibition in Alcohol Use Disorder

INCLUSION CRITERIA

• Alcohol Use Disorder (Minimum 2 symptoms on a validated diagnostic tool e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID)
• Male or female individuals 18-70 years old (inclusive)
• Able to speak, read, write and understand English
• Most recent urine drug test for benzodiazepines, barbiturates, cocaine metabolites, morphine, oxycodone, methadone, amphetamine, & buprenorphine is negative.
• Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is less than or equal to 8

Males only:

-Males agrees agree to sexual abstinence or to use a reliable method of birth control during the study and three months following the last dose of the study drug. Acceptable methods of birth control may include: 1) condom with spermicide; 2) diaphragm with spermicide; or 3) female condom with spermicide.

Females only:

-Women of child-bearing potential may participate in the study:

• if they test negative for pregnancy (based on a urine pregnancy test) prior to initiation of treatment
• they must also agree to use either one highly effective method of contraception or a combination of two effective methods of contraception during the study.
• Highly effective method may include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or/ intrauterine system; vasectomy and tubal ligation.
• Effective methods may include barrier methods of contraception (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge)

Women may choose to use a double-barrier method of contraception. Barrier methods without concomitant use of a spermicide are not reliable or an acceptable method. Thus, each barrier method must include use of a spermicide. It should be noted that the use of male and female condoms as a double-barrier method is not considered acceptable due to the high failure rate when these methods are combined.

OR

-Women not of child-bearing potential may participate in the study and include those who have

• spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications that induced amenorrhea e.g., oral contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy; or
• spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone (FSH) level greater than 40 mIU/mL; or
• women with a history of hysterectomy or bilateral oophorectomy must be at least 40 years of age and FSH >40 mIU/mL.

EXCLUSION CRITERIA

• Lifetime clinical diagnosis of schizophrenia or bipolar disorder
• BMI = 40 kg/m(2)
• History of epilepsy and/or seizures

NOTE: individuals who have a history of alcohol withdrawal seizures may be in the study as long as they have been abstinent from alcohol for at least 2 weeks prior to consent and during that period of abstinence, there were no seizure episodes (otherwise, participant remains not eligible).

• Creatinine greater than or equal to 2 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 times the upper normal limit, hemoglobin 450 msec for men and > 470 msec for women
• Family history of Long QT Syndrome.
• Patients on weight loss medications within 30 days of dosing
• Patients with a history of bariatric surgery
• Diagnosis of diabetes and currently on medication
• Unable to refrain from or anticipates the use of:
• Any drugs known to be significant inhibitors of cytochrome P450 (CYP)3A enzymes and/or P-glycoprotein (P-gp) including regular consumption of grapefruit or grapefruit juice for 14 days prior to the first dose of study medication.
• [medications like acetaminophen (up to 2 g per 24-hour period) and ibuprofen may be permitted during the study]
• Any drugs known to be significant inducers of CYP3A enzymes and/or P-